ABSTRACT The overall mission of the Experimental Therapeutics Program (ET) is to reduce the burden of cancer through preclinical and early clinical drug development; determine optimal treatment combinations and sequences; identify prognostic, predictive and surrogate markers of efficacy and resistance for active agents and deliver best practices to our catchment area and nationally through strategic collaborations. ET encompasses a combination of preclinical, translational and clinical research, with strong ties to the other programs (Breast Cancer [BC], Cancer Prevention and Control [CPC] and Molecular Oncology [MO]). Given its clinical focus, ET has evolved in concert with recent trends and discoveries that have had an impact in the clinic, such as immunotherapy and precision medicine. Aim 1 is focused on targeting known driver pathways of cancer. Aim 2 is focused on targeting the tumor microenvironment (TME) and the immune system. Aim 3 is focused on developing drugs and biomarkers for cancer diagnosis, prognosis and therapy. Significant accomplishments include completing an investigator-initiated trial (IIT) demonstrating the efficacy of pembrolizumab in thymic carcinoma that is shifting the treatment paradigm and work demonstrating the molecular determinants of immune resistance that are identifying new targets for immunotherapy. ET is led by Giuseppe Giaccone, MD, PhD, former Chief of the National Cancer Institute (NCI) Oncology Branch and a leading expert in lung cancer and experimental therapeutics, and Anton Wellstein, MD, PhD, a pharmacologist whose translational research is focused on tumor stromal interactions and mechanisms of cancer progression to metastasis. The LCCC Consortium is comprised of Georgetown Comprehensive Cancer Center, based in Washington, DC (LCCC-DC) and the John Theurer Cancer Center of Hackensack Meridian Health, based in Hackensack, NJ (LCCC-NJ). Accordingly, the LCCC catchment area is defined by the LCCC-DC and LCCC-NJ catchment areas. ET has 43 members, including translational and clinical researchers, from six departments across the Lombardi Comprehensive Cancer Center (LCCC) consortium institutions. The program is funded by $17.81M ($15.84M LCCC-DC, $1.97M LCCC-NJ) in research funding (annual direct costs) of which $1.3M ($0.98M LCCC-DC, $0.32M LCCC-NJ) is peer-reviewed and $0.86M ($0.54M LCCC-DC, $0.32M LCCC-NJ) is NCI funded. ET members published 578 papers, of which 137 were high impact (impact factor [IF] ? 8); 15% interprogrammatic, 23% intraprogrammatic and 48% involving external collaborations with other NCI-designated cancer centers. ET members use all nine LCCC Shared Resources. ET addresses challenges in LCCC?s catchment areas in Washington DC and surrounding counties (LCCC-DC) and Bergen County, New Jersey (LCCC-NJ) by focusing on diseases that are relatively overrepresented, such as pancreatic cancer and lung cancer, and offering research-inspired cancer care to patients, including underserved minorities, throughout these catchment areas.